The most efficient protection against influenza infection is vaccination against circulating strains and it is important to produce influenza viruses for vaccine production as quickly as possible.
Wild-type influenza viruses often grow to low titres in eggs and cell culture. In order to obtain a better-growing virus strain for vaccine production it is currently common practice to reassort the circulating vaccine strain with a faster-growing high-yield donor strain. This can be achieved by co-infecting a culture host with the circulating influenza strain (the vaccine strain) and the high-yield donor strain and selecting for reassortant viruses which contain the hemagglutinin (HA) and neuraminidase (NA) segments from the vaccine strain and the other viral segments (i.e. those encoding PB1, PB2, PA, NP, M1, M2, NS1 and NS2) from the donor strain. Another approach is to reassort the influenza viruses by reverse genetics (see, for example references 1 and 2).
References 3 and 4 report that influenza viruses with a chimeric HA segment which comprises the ectodomain from a vaccine strain and the other domains from A/Puerto Rico/8/34 grew faster in eggs compared to the wild-type vaccine strain. Reference 5 teaches influenza viruses with chimeric NA proteins which contain the transmembrane and stalk domains from A/PR/8/34. References 6 and 7 teach reassortant influenza viruses which comprise chimeric HA segments that have domains from both influenza A and B viruses.
Most of the studies with chimeric HA proteins were done in eggs and reference 3 teaches that “it is likely that the improvement seen with [the described] chimeric viruses is very specific to the egg substrate”. The studies which tested growth in cell culture found that the tested viruses showed poor growth in cell culture. There is therefore still a need in the art to provide high-yielding reassortant influenza viruses, especially in cell culture.